The accessory subunit B of DNA polymerase is required for mitochondrial replisome function
Open accessAbstract
The mitochondrial replication machinery in human cells includes the DNA polymerase gamma holoenzyme and the TWINKLE helicase. Together, these two factors form a processive replication machinery, a replisome, which can use duplex DNA as template to synthesize long stretches of single-stranded DNA. We here address the importance of the smaller, accessory B subunit of DNA polymerase gamma and demonstrate that this subunit is absolutely required for replisome function. The duplex DNA binding activity of the B subunit is needed for coordination of POLgamma holoenzyme and TWINKLE helicase activities at the mtDNA replication fork. In the absence of proof for direct physical interactions between the components of the mitochondrial replisome, these functional interactions may explain the strict interdependence of TWINKLE and DNA polymerase gamma for mitochondrial DNA synthesis. Furthermore, mutations in TWINKLE as well as in the catalytic A and accessory B subunits of the POLgamma holoenzyme, may cause autosomal dominant progressive external ophthalmoplegia, a disorder associated with deletions in mitochondrial DNA. The crucial importance of the B subunit for replisome function may help to explain why mutations in these three proteins cause an identical syndrome.
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The N-terminal domain of Twinkle is important for ssDNA binding and stimulation of the C-terminal helicase activity.
“The N-terminal domain is important for ssDNA binding and stimulation of the C-terminal helicase activity (Farge et al., 2007).”
From Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases (2017) · cites this paper as Farge et al., 2007
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- Authors
- Farge, G., Pham, X. H., Holmlund, T., Khorostov, I., & Falkenberg, M.
- Affiliations
- Karolinska Institutet (SE)
- Corresponding author
- Falkenberg, M.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-01-26
- Volume
- 35
- Issue
- 3
- Pages
- 902-911
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC1807957
- OpenAlex
- W2001294987
- Cited by
- 62
- References
- 24
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 3 · 2022: 1 · 2021: 4 · 2020: 3 · 2019: 4 · 2018: 2 · 2017: 2 · 2016: 4 · 2015: 4 · 2013: 4 · 2012: 4
- FWCI
- 2.12
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- Nucleic Acids Research (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- European Commission
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Keywords
- DNA polymerase gamma, Twinkle helicase, mitochondrial DNA replication, DNA duplex binding, chronic progressive external ophthalmoplegia, mitochondrial DNA deletions
- MeSH terms
- DNA Polymerase gamma, Replisomes, DNA, DNA-Directed DNA Polymerase, DNA Replication, DNA Helicases, DNA, Mitochondrial, DNA, Single-Stranded, Humans, Multienzyme Complexes, Mutation, Templates, Genetic, Protein Subunits, Mitochondrial Proteins
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